4122-79-6Relevant articles and documents
Innovative Disulfide Esters of Dithiocarbamic Acid as Women-Controlled Contraceptive Microbicides: A Bioisosterism Approach
Mandalapu, Dhanaraju,Lal, Nand,Kumar, Lokesh,Kushwaha, Bhavana,Gupta, Sonal,Kumar, Lalit,Bala, Veenu,Yadav, Santosh K.,Singh, Pratiksha,Singh, Nidhi,Maikhuri, Jagdamba P.,Sankhwar, Satya N.,Shukla, Praveen K.,Siddiqi, Imran,Gupta, Gopal,Sharma, Vishnu L.
, p. 1739 - 1753 (2015)
In an ongoing effort to discover an effective, topical, dual-function, non-surfactant contraceptive vaginal microbicide, a novel series of 2,2′-disulfanediylbis(3-(substituted-1-yl)propane-2,1-diyl) disubstituted-1-carbodithioates were designed by using a bioisosterism approach. Thirty-three compounds were synthesized, and interestingly, most demonstrated multiple activities: they were found to be spermicidal at a minimal effective concentration of 1-0.001 %, trichomonacidal against drug-susceptible and resistant Trichomonas strains at minimal inhibitory concentration (MIC) ranges of 10.81-377.64 and 10.81-754.14 μM, respectively, and fungicidal at MIC 7.93-86.50 μM. These compounds were also found to be non-cytotoxic to human cervical (HeLa) epithelial cells and vaginal microflora (Lactobacilli) in vitro. The most promising compound, 2,2′-disulfanediylbis(3-(pyrrolidin-1-yl)propane-2,1-diyl)dipyrrolidine-1-carbodithioate (5), exhibited spermicidal activity 15-fold higher than that of the marketed spermicide Nonoxynol-9 (N-9) and also demonstrated microbicidal potency. To identify common structural features required for spermicidal activity, a 3D-QSAR analysis was carried out, as well as in vivo efficacy studies and fluorescent labeling studies to determine the biological targets of compound 5. Change it out: A series of disulfide esters of dithiocarbamic acid were synthesized to block free sulfhydryl groups present in sperm and Trichomonas for a safe dual-action spermicide. A majority of the compounds demonstrated multiple activities with good safety profiles, with the most promising compound exhibiting spermicidal activity 15-fold higher than that of the marketed spermicide Nonoxynol-9.
PREPARATION AND PHARMACOLOGICAL PROPERTIES OF SOME
FAILLA,MASSAROLI,SCURI,SIGNORELLI
, p. 269 - 285 (2007/10/04)
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